Use of a polarized field to modify the efficacy of a bioactive agent

ABSTRACT

A bioactive agent ( 53 ) is administered to a patient ( 1 ), and the efficacy of the bioactive agent ( 53 ) is modified by exposing the patient ( 1 ) to a polarizing field ( 39, 41, 52 ). The bioactive agent ( 53 ) may be a chemotherapeutic agent administered to a patient with cancer, and the polarizing field ( 39, 41, 52 ) may be an electric field and/or a magnetic field. The direction and/or strength of the polarizing field ( 39, 41, 52 ) may be changed during treatment to promote the opportunity for enhanced therapeutic interaction between the bioactive agent ( 53 ) and the field ( 39, 41, 52 ).

This application is a national phase application based upon PCTApplication Ser. No. PCT/US/96/12361, filed on Jul. 26, 1996, whichclaims benefit to Provisional patent application Ser. No. 60/001,719,filed on Jul. 28, 1995.

TECHNICAL FIELD

The invention relates to the electrophysiology of the human body. Morespecifically, the invention provides methods of altering normal chargedistribution within selected areas of the body to increase theeffectiveness of bioactive agents such as drugs in these areas.

BACKGROUND ART

Modern medical practice includes the application of electromotive force,defined by the Handbook of Chemistry and Physics, 39th Edition, as “thatwhich causes a flow of current”, to the body in several beneficialtechniques. For example, pharmacological agents are delivered to, orreleased at, target sites within the body through the use of currentflow, either between electrodes or induced by oscillating or pulsingelectric or magnetic fields which alternately push and pull electronswithin the body structure. Balkiston's Gould Medical Dictionary(McGraw-Hill) defines these techniques as:

Iontophoresis: a method of inducing therapeutic particles into skin orother tissue by means of electric current.

Electrophoresis: the migration of charged colloidal particles throughthe medium in which they are disbursed when placed under the influenceof an applied electric potential.

Electroosmosis: the movement of a conducting liquid through a permeablemembrane under the influence of a potential gradient, thought to becaused by the opposite electrification of the membrane and liquid.

U.S. Pat. Nos. 4,141,359 and 5,336,168 show representative methods ofthese technologies.

In another medical use of electromotive force, direct or induced currentflow is used to promote bone healing. U.S. Pat. Nos. 4,683,873 and4,993,413 show representative methods of this technology.

In still another medical use of electromotive force, direct or inducedcurrent flow is used for “electrostimulation” of nerves to mask pain.U.S. Pat. Nos. 5,342,410 and 5,397,338 show representative methods ofthis technology.

The foregoing uses of electromotive force in medicine all involve a flowof current, or continuous movement of charge carriers (i.e., electronsor ions) through a conductive medium under the influence of an electricfield that is maintained in the medium by contact with a power source.Unless an electric field within a conductor is maintained by a powersource, however, the field and thus also the current will drop to zeroregardless of the field outside the conductor. This is a well known andaccepted tenet of basic physics. In regard to conductive biologicalsystems, some researchers in the field have predicted, on a theoreticallevel, that an external electric field with no conductive connection tothe body is reduced to such a degree inward of the surface of a humanbody that it has been commonly believed that an external electric fieldalone could have little effect inside the body. For example, oneresearcher has used Maxwell's equations with certain boundary conditionsto mathematically predict that a static electric field passing inside aliving organism is rendered one trillion times smaller inside theorganism than the same field outside the organism. Also, the sameequations have been employed to support a prediction that the electricfield portion of a 60 Hertz electromagnetic field is rendered 40 billiontimes smaller inside a living organism than the same field outside theorganism (CRC Handbook of Biological Effects of Electromagnetic Fields,CRC Press, pages 5-9, 1986).

As a result of this common belief concerning abrupt reduction of anexternal electric field at the surface of a living organism, thequestion of whether such a field may have biological effects on livingorganisms has received little attention.

A magnetic field, on the other hand, is able to penetrate into aconductor. Unlike external electric fields, magnetic fields have a rolein the modern practice of medicine. For example, large magnets are usedin nuclear magnetic resonance imaging systems.

A magnetic field can have biological consequences. Researchers havereported that a magnetic field can alter the growth of bacteria andyeasts. Researchers have also reported that a magnetic field can alterenzyme activity in vitro, particularly if the field is non-uniform.Furthermore, researchers have reported that a magnetic field reduces theability of protozoa to survive exposure to a toxic substance. See theCRC Handbook of Biological Effects of Electromagnetic Fields, supra, atpages 173-175.

The prior art does not contemplate the use of static electric or staticmagnetic fields to increase the effectiveness of bioactive agents byaltering the receptivity or susceptibility of cells, or othertherapeutic targets such as bacteria or viruses for example, to suchagents. These methods form the basis of the invention.

DISCLOSURE OF THE INVENTION

It is now recognized that every action in every living organism,including the human body, results from electric charges and theirattendant electric fields. Each of the approximately seventy-fivetrillion cells in a human body utilizes specific patterns of electriccharges to create specific patterns and strengths of electric fields on,within, and around the cell membranes and interior components to carryout the various processes required to maintain life. Abnormal chargedistributions can lead to an inability to properly carry out normalprocesses and result in maladies ranging from aches and pains to seriousdisease. Such maladies, and even a genetic susceptibility to suchmaladies, shall be referred to herein as “disease conditions”.

The drugs and other bioactive agents that are administered to treat suchmaladies have molecules with a specific electron arrangement whichprovides a specific electric field. Organic materials such as cells inthe human body likewise have chemical constituents with specificelectron and electric field arrangements, as do pathogens and toxins.The reason a particular bioactive agent is effective in treating aparticular disease is generally that the specific electron and electricfield arrangement exhibited by the bioactive agent interacts, in acomplimentary fashion, with the specific electron and electric fieldarrangement exhibited by a site on a therapeutic target, such as humancells, enzymes, bacteria, and so forth. This interaction alters thenature of the target in a manner that is beneficial to the patient. Forexample, a bioactive agent may have an electrical configuration whichinteracts with that at some location of a human cell to cause the agentto accumulate near, or attach to, a specific receptor on or in the cell.This, at least temporarily, beneficially alters the cell, or the cell'soperation, or aids the cell in carrying out normal processes. Thisdependence on specific electron and field strength patterns is thereason bioactive agents are effective against some maladies and notothers. This is also the reason some agents are only marginallyeffective, i.e., the electron pattern and resulting field strength ofthe agent's molecules are not quite right for optimum attraction of, andconnection with, a therapeutic target giving the desired result. It isalmost universally desirable to increase the effectiveness, or increasethe range of effects, of the bioactive agents in the medicalpharmacopoeia.

The inventor has discovered that exposing the body, or specific desiredareas of the body, to a static electric field or to a static magneticfield can significantly increase the effect of some bioactive agents onthe body. Presumably these fields act to slightly alter or strengthenthe electric charge distribution pattern near, on, or within the exposedbody cells, and thus increase the receptivity or susceptibility of thecells to reaction with the bioactive agent. Also, there is reason tobelieve that using static electric or static magnetic force fields toalter the normal electric charge distribution near, on, or within theexposed cells may in addition cause the cells to prematurely initiatesome of their normal metabolic operations and thus place them in acondition which increases their receptivity or susceptibility to appliedbioactive agents.

The term “static electric field” as used herein is intended to meanfields from an electrical potential which maintain the same polarityover a period of time of at least 1 second, but more commonly overminutes or hours. The term “static magnetic field” as used herein isintended to mean fields from a magnetic element which maintain the samepolarity over a period of time of at least 1 second, but more commonlyover minutes or hours.

Static electric and static magnetic fields will occasionally be referredto collectively herein as “polarizing fields.” This nomenclature isbelieved to be appropriate since a nonpolar particle such as a moleculein an electric field may become polarized by induction, and the dipolemoment or degree of polarization of an inherently polarized particle ismodified by a static electric field. The mere presence of a staticmagnetic field does not induce or modify polarization, but a staticmagnetic field is nevertheless appropriately characterized as apolarizing field in the context of the invention since the degree ofpolarization of an inherently polarized particle which moves withrespect to a magnetic field is modified by the magnetic field. For aliving body, such movement is to be expected.

According to the invention, a bioactive agent is administered to apatient and the patient's body or a target region thereof is exposed toa polarizing field without producing current flow or heat, as wouldoccur if the patient's body were made to be part of an electric circuit,or exposed to moving magnetic fields, as in the prior art. Instead, thepolarizing field is applied to achieve a polarizing effect within thetissue, creating dipoles from particles such as atoms, ions, ormolecules in, on, or near the components of the tissue, or modifying thecharge distribution of such particles if they are inherently polarized,to achieve enhanced reaction with a desired bioactive agent. Dependingon the components of the tissue, the polarizing field applied, and thebioactive agent, the individual components and/or bioactive agent may beinfluenced in a number of ways, for example they may:

shift their electron distribution to favor reaction.

shift their electron distribution to create charge gradients favoringattraction of, and reaction between, the components and bioactiveagents.

rotate to expose a surface favoring reaction.

move to a location (within the cell membrane for example) favoringreaction.

prematurely initiate a normal activity or process of the cells or othercomponents which favors reaction with the desired bioactive agent.

A polarizing field is applied with the polarizing force in one directionlong enough to achieve any, or any combination of, the above actions.Typically the polarizing force direction of the applied field will bemaintained for at least numbers of seconds, but most often for numbersof minutes or hours, or continuously, during the treatment period. Theforce direction may also be periodically changed to provide additionalopportunities for cellular reaction.

The steps in using the invention may vary to meet the requirements ofspecific bioactive agents, or specific locations of a patient's body.Most often, the steps will include:

1. Administering the desired bioactive agent or agents to the patientthrough any medically approved route.

2. While the agent is present in the body (even as the agent is beingadministered, if desired) exposing at least a target region of the bodyto a polarizing field.

3. Continuing the polarizing field exposure for a length of time basedon the active life of the bioactive agent, or at least a portion of theactive life, such as half-life, for example.

4. Discontinuing the exposure to the polarizing field after the desiredeffect has occurred, or at a point based on the active life of thebioactive agent.

It is an object of the invention to increase the effectiveness of abioactive agent or agents administered to the body by exposing the wholebody, or a selected target region of the body, to a nonuniform, or to arelatively uniform, polarizing static electric and/or static magneticfield.

Another object of the invention is to increase the effectiveness of abioactive agent or agents administered to the body by exposing all ofthe body, or a selected target region of the body, to a nonuniform, orto a relatively uniform, polarizing static electric and/or staticmagnetic field long enough to influence charge distribution near, on, orwithin the exposed cells to increase the receptivity or susceptibilityof the cells to interaction with the bioactive agent by increasingattraction of the agent to locations on and/or in the cells, and/or byinitiating or preventing a metabolic process of the cells in thepresence of the agent.

Another object of the invention is to increase the effectiveness of abioactive agent or agents administered to the body by exposing all ofthe body, or a selected target region of the body, to a nonuniform, orto a relatively uniform, polarizing static electric and/or staticmagnetic field, long enough to influence charge distribution near, on,or within exposed cells to increase the receptivity or susceptibility,or initiate or prevent metabolic processes, of the cells so as tooptimize interaction with the bioactive agent at some location of thecells, then changing the direction of the polarizing field one or moretimes to create the same conditions and reactions at other locations ofthe cells.

Another object of the invention is to increase the effectiveness of abioactive agent or agents administered to the body by exposing all ofthe body, or a selected target region of the body, to a nonuniform, orto a relatively uniform, polarizing static electric and/or staticmagnetic field with sufficient amplitude (strength) to influence thecharge distribution near, on, or within exposed cells so as to increasethe receptivity or susceptibility of the cells to interaction with thebioactive agent by increasing the attraction of the agent to locationsof the cells and/or by initiating or preventing a metabolic process ofthe cells in the presence of the agent.

Another object of the invention is to increase the effectiveness of abioactive agent or agents administered to the body by exposing all ofthe body, or a selected target region of the body, to a nonuniform, orto a relatively uniform, polarizing static electric and/or staticmagnetic field of one amplitude (strength) to influence the chargedistribution near, on, or within exposed cells to a certain degree, andby then increasing and/or decreasing the amplitude one or more times toinfluence the charge distribution near, on, or within exposed cells toanother degree, so as to increase the receptivity or susceptibility ofthe cells to interaction with the bioactive agent by increasingattraction of the agent to locations of the cells and/or by initiatingor preventing metabolic processes of the cells in the presence of theagent.

It is another object of the invention to increase the effectiveness of abioactive agent or agents administered to the body by exposing all ofthe body, or a selected target region of the body, to a nonuniform, orto a relatively uniform, polarizing static electric and/or staticmagnetic field creating charge gradients near, on, or within exposedcells to increase the receptivity or susceptibility of the cells tointeraction with the bioactive agent by increasing the attraction of theagent to locations of the cells and/or by initiating or preventing ametabolic process of the cells in the presence of the agent because of aparticular charge level so created at some location on, near, or withinthe cells.

It is another object of the invention to use any combinations of themethods of the above noted objects to increase the effectiveness of anybioactive agent or agents administered to the body in the presence of apolarizing field.

These objects, as well as other objects, which will become apparent inthe following discussion, may be selectively achieved singularly or inany combination, and the invention may be practiced with one orcombinations of bioactive agents. The result is a highly desirableincrease in action of the bioactive agent, or agents, which can increasetheir therapeutic potency, even to the point of requiring less bioactiveagent if desired. Also, if desired, the increased action of thebioactive agent may be restricted to only certain areas of the body,thus reducing what may be undesired action of the agent or agents in oron other areas of the body. In addition, the increased action of thebioactive agent may result in agents which were formerly only marginallyeffective becoming effective enough for beneficial use.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a perspective view of a patient undergoing total body exposureto a static electric field after receiving a bioactive agent, inaccordance with one embodiment of the invention;

FIG. 2 is a cross-sectional view illustrating a portion a treatmentelement shown in FIG. 1;

FIG. 3 is a block diagram of an embodiment of a power supply systemwhich can be used with the arrangement shown in FIG. 1;

FIG. 4 is a block diagram of another embodiment of a power supplysystem;

FIG. 5 is a block diagram of yet another embodiment of a power supplysystem;

FIG. 6 is a side elevational view showing one embodiment of a treatmentelement and an optional additional treatment element for exposing atarget region of the body to an electric field;

FIG. 7 is a elevational view showing an embodiment of an insulatedconductive element inside a body cavity;

FIG. 8 is a side elevational view showing a patient undergoing totalbody exposure to a static magnetic field, due to permanently magnetizedelements, after receiving a bioactive agent;

FIG. 9 is a cross-sectional view illustrating a portion of an embodimentof a static magnetic field treatment element which can be used in thearrangement shown in FIG. 8;

FIG. 10 is a cross-sectional view illustrating a portion of anotherembodiment of a static magnetic field treatment element which can beused in the arrangement shown in FIG. 8;

FIG. 11 is a side elevational view showing a patient undergoing totalbody exposure to a static magnetic field from direct current drivenelectromagnet elements after receiving a bioactive agent;

FIG. 12 is a cross-sectional view illustrating a portion of anembodiment of a static magnetic field treatment pad which can be used inthe arrangement shown in FIG. 11; and

FIG. 13 is a side elevational view showing a patient who has received abioactive agent and who is being exposed to a static magnetic field at atarget region where magnetic, or magnetizable, material has beenapplied.

MODES FOR CARRYING OUT THE INVENTION

The invention arises from the inventor's discovery that the efficacy ofa bioactive agent which has been administered to a mammal can bemodified by exposing the mammal to a polarizing field (that is, a staticelectric field or a static magnetic field, or both). This discovery isbased on experiments with mice which the inventor has conducted. Butbefore either the experiments or specific practical embodiments of theinvention are described, a theoretical discussion will be offered in aneffort to aid in understanding and practicing the invention. However, itmust be recognized that our knowledge of cellular operation at themolecular level is incomplete. For example, it is not currently possibleto accurately predict the effect of chemical agents on cells, so massscreenings are used to identify drug candidates. Also, it is notcurrently understood how most cell processes, including major processessuch as differentiation or division, are initiated or controlled. Thediscussions here are therefore not intended to be limiting on theinvention in any manner.

Every process of life is an electrochemical reaction occurring near, on,or within the cells. We now know that cell membranes are bimolecularlayers of lipid molecules, with polar groups on the molecules orientedtoward the inner and outer surfaces of the membrane. The membrane has athickness of only about forty molecules and includes structures, such aschannels to intake or exhaust materials for example, and also hundredsto thousands of protein macromolecules either imbedded in or extendingthrough the membrane. The membrane can be described as a “fluid mosaic”in which many (if not all) of the macromolecules can move around themembrane over time to different locations, and the exact location andconfiguration of many of these macromolecule can change either as afunction of, or to cause, cellular activities.

The interior of the cell is even more complex. The interior containscytoplasmic fluid subdivided into many compartments by various types oforganelles, each of which has specialized functions in cell activities.Also, the interior of the cell is criss-crossed with a complexcytoplasmic matrix of filaments and microtubules which span between themembrane and organelles, and which are believed to play a key role incontrolling cellular activities.

In total, cells have an extremely complex structure and are formed frommostly nonconductive but electroactive lipid or protein molecules, eachwith unique electric charge distributions and thus emanating uniqueelectric field patterns around the molecules. The electric fields ofindividual cell molecules combine with the electric fields ofneighboring molecules, in either strength increasing or decreasingfashion, to initiate or control activities of the cell. In addition tothe electric fields on or within individual cells, the cells aremaintained in close relationship to adjacent cells in thethree-dimensional structure of tissue, and the electric fields of all ofthe cells combine in either a strength-increasing or strength-decreasingfashion.

Quoting from the book Bioelectronics, by Stephen Bone and Bogumil Zaba(John Wiley, & Son, 1992, page 6), “We must therefore, howeverreluctantly admit that the prediction of the behavior of even thesmallest protein, containing as it does some thousands of atoms, from aconsideration of its electronic structure is a long, long way beyond ourcurrent capabilities”. The complex interaction of electric fields near,on, and within cells of the body makes it difficult, and currently mostoften impossible, to determine what initiates what and what controlswhat. However it is known that natural or synthetic drugs or otherchemical molecules, herein collectively described as bioactive agents,approach, align with, enter and/or react with cells based oncomplimentary electric charge distribution patterns of the cell and thebioactive agent molecule.

Cell membranes present a charged surface, based on the existing locationand condition of the molecules on and within the cell, with the chargefield extending out into the body fluids in the space between cells.Under most methods of administering bioactive agents to the body, bodyfluids serve to carry the agents throughout the body and to locationsnext to the desired cell membranes. Under the combined influence of thespecific electric field pattern of the bioactive agent and the specificelectric filed pattern at a receptor site, on or in the cell, mostbioactive agents operate by bonding with the cell to either elicit aresponse from, or prevent an action of, the cell. Bioactive agents usedagainst bacteria and viruses generally operate in the same manner.

As was noted previously, the inventor has discovered that a polarizingfield, applied to the body while a desired bioactive agent is present,can modify the efficacy of the bioactive agent's reaction with cells.This modification can be an increase in the potency of the bioactiveagent to such a significant degree that measurable results are obtainedfar above those created by the bioactive agent alone. How this effectoccurs is not currently understood, but may be the result of one or acombination of the following three mechanisms:

1. The applied field may be interacting with and reinforcing orstrengthening some normal charge distribution near, on, or within thecells, which results in strengthened attraction and affinity for thebioactive agent. In addition, this stronger attraction may cause morethan a normal amount of the bioactive agent to accumulate in the bodyfluid between cells in the region of the applied field and thus be moreavailable for reaction.

2. The applied field may be attracting or repelling the normal chargedistribution near, on, or within the affected cells to an extent thatrearranges the cell's receptor area charge distribution to a morefavorable pattern for attracting and reacting with the bioactive agent.This may even include rotating, or moving, macromolecules of the cell,most particularity within or on the cell membrane, to new locations.

3. The applied field may be changing the normal charge distributionnear, on, or within the cells in a manner which causes a normal actionof the cells to occur prematurely or at an increased rate, and whichincreases the cell's receptivity or susceptibility to the bioactiveagent. One such action could be the activation of “voltage-gated”channels, known to exist in cell membranes, which normally open andclose to allow required ion passage in and out of the cells for cellmetabolism, but in this case would allow increased passage of thebioactive agent to the cell's interior.

Regardless of the mechanism, the invention can be used to increase thecurrently known efficiency or potency of bioactive agents in relation tothe treatment of various conditions and maladies. In addition, it isbelieved that the invention can provide beneficial use options beyondthose currently available for some bioactive agents. For example:

1. Bioactive agents are administered in dose sizes known to create thedesired therapeutic effect. Many bioactive agents are very expensive,and using the invention in conjunction with these agents may permitsmaller doses of the agent achieve the desired effect.

2. Some bioactive agents have a therapeutic index in which the requireddose size, for a desired therapeutic effect, is also close to the toxicdose size. Use of the invention with these agents may allow smaller dosesizes to achieve the desired effect with less chance of toxicity.

3. Response time to achieve the ultimate desired effect after bioactiveagents are administered to the body depends on many factors, however useof the invention with the agents may decrease the response time.

4. Some bioactive agents are only marginally effective against someconditions or maladies, but provide the only currently availabletreatment. Use of the invention with these agents may improve thetreatment outcome.

5. Some bioactive agents must be administered by routes which involvethe whole body because of their particular toxic, caustic, or otherproperties, yet their therapeutic target may be only a small region orlocation of the body. Use of the invention at one or more desiredregions of the body along with these agents may allow a smaller wholebody dose size to be as effective as the normal larger dose, but only inthe region of the therapeutic target, and thus decrease detrimentaleffects of the agent on the rest of the body. Alternately, the normallarger whole body dose size may be given, with the invention being usedto increase the action of the bioactive agent in only a desired bodyregion, to improve treatment there while sparing the rest of the bodyfrom the increased potency of the bioactive agent/polarizing fieldcombination.

6. Some bioactive agents have a short effective life when administeredto the body because they react with various chemicals and enzymes of thebody and quickly degrade. Use of these agents according to the inventionmay help their desired effect to occur before they degrade.

Although there is every reason to believe the invention will beeffective with many bioactive agents and diseases, the inventor'scurrent research has centered on cancer treatment. This is aparticularly important area for improvement because tumor regression andfive year survival rates are unacceptably low in many types of cancer.Also, most current chemotherapy treatment regimens repetitively exposethe whole body to bioactive agents just as capable of destroying manytypes of body cells as they are capable of destroying tumor cells. Afine line is walked in these regimens. The chemotherapy agents are givenin large enough dosage, often enough, to hopefully cause tumorregression without doing more damage to the body than the cancer.

One example of use of the invention in cancer treatment would be toapply a polarizing field to increase the efficacy of thechemotherapeutic agents only in the region of the body with the tumor.This would make a standard dose regimen more potent only in the area ofthe cancer, thus increasing efficacy in this area while sparing the restof the body from the increased potency. Alternately, this approach mayallow the use of smaller dose regimens which spare the rest of the bodyfrom the detrimental effects of the standard larger dose regimens, butprovide the efficacy of the larger regimens in the cancer location.

The inventor's research model has been the B6C3F1 mouse strainrecognized by the National Cancer Institute as one Standard forchemotherapy research, and is one of the commonly accepted rodentspecies used in transplantable tumor studies. For the inventor'sstudies, female mice were implanted with murine mammary 16/Cadenocarcinoma, a commonly accepted tumor for breast cancer research,and the growth rate of the tumors in Control Groups was compared to thatof Test Groups which were under the influence of a polarizing field (upto 11 animals in each Group). Each study was designed to be as uniformas possible. In particular:

All test animals were approximately six weeks old, with a body weight of17 to 20 grams at the time of implant.

Food and water were provided ad libitum throughout each study, and allGroups were exposed to the same temperature and light conditions (lightson 12 hours and off 12 hours each day).

Tumor measurements were made either by caliper, using the prolateellipsoid formula of the National Cancer Institute, or by removing thetumor mass and weighing to 0.01 gram. The method chosen was used for allanimals in each study.

Since no existing experimental protocol covers studies of this type, theinventor used altered guidelines from the National Cancer Institute'ssubcutaneously implanted tumor protocols #3C872 and #3CDJ2. In essence,approximately equal-sized tumor fragments were implanted in each mouse'saxillary region through a puncture in the inguinal region. The tumorgrowth rate was then compared between groups of untreated controlanimals (no chemotherapeutic agent or polarizing field applied), orgroups of treated control animals (treated with chemotherapeutic agentonly), and groups of test animals (polarizing field and chemotherapeuticagent applied) by measuring, or removing and weighing, the resultingtumors over time. The 16/C murine mammary tumor used is particularlyaggressive, and can normally grow from a barely visible, or eveninvisible, bump under the skin the day after the implant, to 10 to 20percent of the animal's total body weight by day 14 (tumor sizetypically up to 4 grams). The tumor size for individual animals variesas the tumors grow, but the median tumor size of all groups can normallybe expected to be relatively uniform if each group is set up to containequal numbers of visible tumors of approximately equivalent size the dayafter the implant. After clipping the hair over the tumor site forproper inspection, the animals were divided into Groups withapproximately equal tumor sizes, and a random number generator, ordrawing by lot, was used to randomly assign the status of each Group asControl or Test. Extrapolating from the #3C872 Protocol, a Test Groupwith a median tumor weight deviating 42 percent or more from the ControlGroup (Test/Control, or T/C), on days 12 to 16, was considered todemonstrate abnormal (faster or slower) tumor growth. Tumor regressionrates were also charted in some of the studies.

The mice in each Test Group were subjected to polarizing fields with theuse of special cages or holders. The inventor has used several cagedesigns, depending on the goal of the particular study. All cages wereconstructed from polyethylene storage boxes, either 19.5 quart “Keepers”boxes from Rubbermaid Corporation, Wouster, Ohio (#2222), or 66 quart“Clear View” boxes from Sterilite Corporation, Townsend, Mass. (#1758).Other components used in the various cage types or holders will be notedin the following Study Examples, and include:

Styrene grid: a ⅜″ thick plastic grid with ½″ open squares (NationalHome Center, Plaskolite Egg Crate Light Diffuser #74507-43200).

Hardware cloth: a ¼″ grid of galvanized #23 gauge wire (G. F. Wright &Wire Company, Worester, Mass., #21936-00491-7).

Acrylic sheet: either ⅛″ or ¼″ clear plexiglas (Cope Plastics, LittleRock, Ark.).

Screen wire: standard aluminum screen wire (local source).

Aluminum foil: Reynolds Wrap Heavy Duty (local source).

The inventor's series of studies have involved exploring the effect of astatic electric field alone on cancer cell growth rates. Although abioactive agent was not administered to the mice in this series ofstudies, the nutrient ions and other chemicals in the body fluidsnormally used by the cells served than analogousis purpose. The resultswere surprising, and a couple of examples are included below. Also, theresults of other studies of this type are included in the inventor'scopending patent application, “Intimately Worn Items for Protection fromBiological Interaction with Electrostatic Fields”, Ser. No. 08/488,198,the disclosure of which is included in that application is includedherein by reference.

EXAMPLE A

Mice can generate significant electrostatic charges if their fur rubsover a surface. For example, after rubbing the back of mice over sixinch square material samples (about a five inch rub path), the inventormeasured charges on various materials of:

Polyethylene Grid, −2,370 volts Glass, −220 volts Styrene Grid, +1,970volts Aluminum Plate, −100 volts Acrylic Plastic, −1,820 volts HardwareCloth, −230 volts

In each of these examples, as reflected by the law of chargeconservation, equal but opposite polarity charges were generated on thesurface of the animal's fur.

This effect was used in tests to generate static electric charges onmice as they moved around in cages, and the resulting tumor growth ratecreated by exposure to the polarizing fields of these charges wasmeasured. In one example of this, tumor growth rates in Control Groupsof mice, in minimum-charge-generating cages, were compared to tumorgrowth rates of Test Groups in cages with surfaces capable of generatingstatic electric charges. After implanting the mice with tumors, theinventor set-up four groups of mice (11 animals in each group) withapproximately equivalent tumor burdens in each group, in four 66 quartcages. The cages were then randomly assigned to the study methods. TheGroup A (control group) cage contained only a wire cage floor. The GroupB cage contained a wire grid floor, and also a piece of polyester carpetsuspended above the floor with the carpet fiber ends 1″ above the floor,and also the carpet surface was coated with a conductive (but dry)mixture of 3% Exxon Q-14-2 cationic surfactant to quickly disperse anyelectrostatic charges generated. The Group C cage contained a wire gridfloor plus polyester carpet (uncoated) suspended 1″ above the floor. TheGroup D cage contained a plastic grid floor plus a piece of polyestercarpet (uncoated) suspended 1″ from the floor. The study design thusallowed the mice in Groups A and B to generate only low levelelectrostatic charges as they moved around in the cages, while Groups Cand D created much higher charges as their fur rubbed against thenonconductive carpet above them. Electrostatic field measurements weremade each day in each cage and typically found field levels around 200volts in the Group A and B cages, and around 1,500 volts in the Group Cand D cages.

The animals were placed in their respective cages four days after thetumor implant, and tumor size measurements were made on days 4, 7, 10,and 13. The median tumor size (in milligrams) and the ratio of each TestGroup tumor to the Control Group (ratio shown in parentheses) is shownin TABLE 3:

TABLE 3 Group Day 4 (start) Day 7 Day 10 Day 13 A. 36.5 mg 37.0 mg 119.8636.0 mg mg B. 39.5 (8%) 59.6 (65%) 162.7 619.0 (−3%)  (35%) C. 43.5(19%) 98.4 (165%) 358.2 1,548.0 (143%) (199%) D. 41.6 (14%) 104.6 (183%)362.4 1,459.0 (129%) (202%)

The median tumor size of the weak electrostatic field-exposed Groups Aand B remained very similar throughout the study. The median tumor sizeof the stronger electrostatic field-exposed Groups C and D also remainedvery similar throughout the study, but by day 13 the tumors in bothGroups C and D were close to 2.5 times larger than the tumors in GroupsA and B.

The inventor conducted a statistical analysis of the results usingFisher's Exact Tests, and Mann-Whitney U tests comparing the tumorgrowth in combined Groups A and B, with that of combined Groups C and D.As usual, a p-value of 0.05 or less was considered a significantdifference between the Groups. None of the Groups showed a significantdifference on day 4 at the start of the study. In terms of absolutetumor size, the Fisher test indicated significant group differences ondays 7, 10, and 13 (p=0.034, 0.006 and 0.034 respectively). In terms ofchanges from day 4, the Fisher test indicated significant Groupdifferences on days 10 and 13 (p=0.034 in each case) but not on day 7(most likely due to the fact that Group B had a number of tumors abovethe overall median). With the Mann-Whitney test, absolute tumor size wassignificantly different on days 7, 10, and 13 (p=0.012, 0.007, and 0.010respectively), and the changes from day 4 were also significant for allthree days (p=0.023, 0.006, and 0.012 respectively). The Mann-Whitney Uscores were then converted to odds of a CD animal having a larger tumorsize increase than an AB on each day: day 7=2.34 to 1, Day 10=2.84 to 1,and day 13=2.86 to 1.

EXAMPLE B

To have better control over the strength and location of the electricfields used in the inventor's studies, much of his research has involvedplacing known electric charge levels on conductive surfaces, aboveand/or below the animals in the cages, to provide controlled exposure ofthe animals to electric fields from these charged surfaces (the animalscould not contact the charged surfaces). Model #MP power supplies fromSpellman High Voltage Electronics Corporation, Plainview, N.Y., wereused for these studies because they provide very low output ripple, andprovide a suitable static electric charge.

The inventor has conducted studies placing the Test Group mice inelectric fields of various strength between charged and groundedsurfaces, and compared their median tumor weight growth to Control Groupmice in the same type of cage but with no electric field applied. In thefollowing example, to explore the extreme level of accelerated tumorgrowth possible from exposure to a static electric field, after tumorimplant a Control Group and a Test Group of mice were placed in 19.5quart cages. Each cage had a styrene grid laid on the normal floor tokeep the animals out of their wastes, and a top sheet of ⅛″ thickacrylic, with electrically grounded aluminum foil covering the surfaceaway from the animals, was animals suspended 1⅞″ above the grid floor.The Control Group cage contained hardware cloth covering all plasticsurfaces to minimize charge generation. An aluminum plate was placedunder (outside) the Test Group cage and charged to negative 14,850 voltswith a Spellman power supply to expose the Test Group mice to a strongelectric field. The study was terminated on day 16, and the median tumorweight of the Test Group was 344% larger than the Control Group.

The results of the studies reported above, and those in the notedcopending application, are surprising since, although possiblebiological effects of electromagnetic fields have received considerableattention. It has been generally assumed heretofore that a staticelectric field (the type of polarizing field used in the above studies)cannot exert influence in biological tissue due to the electricalconductivity of fluid in the tissue. This assumption is erroneous, as isevident from the inventor's studies; cancer cells within a mouse couldnot be effected by a static electric field if the field were entirelyincapable of acting within the mouse's tissue. The erroneous assumptionwas presumably based on a principle of physics known as Gauss' law(which can be used to show that the electric field inside a perfectlyconducting object is necessarily zero, unless energy is expended tomaintain a voltage difference across the object). The results of theinventor's research do not disprove Gauss' law, of course, but insteadmake it evident that a living body cannot be viewed conceptually as aperfect conductor.

A possible theoretical explanation for the results reported above may bethat a living organism is far from the homogenous conductive sphere orother shape typically used in physics classes to illustrate a zeroelectric field inside of a conductive object. Also, the tissue structureand dynamic, continually changing, electrochemical operation of a livingorganism may be far too complex to model with Maxwellian equations. Aliving organism is not homogeneous. For example, humans areapproximately 60% water, with electrolytes to make it conductive, but40% of the body is constructed of proteins and lipids, which rank amongthe best nonconductors on earth. This nonconductive 40% is the importantpart, and may also provide paths through which a static electric fieldis able to exert orientating influence into a body and effect normalmetabolic activities. In any animal body, if the atoms and molecules ofthe nonconductive membranes of the skin cells are polarized by anexternal electric field, these atoms and molecules would become electricdipoles, with their normal electron distribution rearranged to create anelectric field imbalance which could in turn be transmitted to adjacentcells. Each cell in the solid tissue of the body makes a number of typesof intimate connections with adjacent cells, including tight junctions,desmosomes, and gap junctions. In addition, there is an extensivenetwork of interstitial fibers, constructed of protein, connectingbetween cells and helping, in effect, to hold the body together. Also,there is an extensive network of nonconductive microtubules and strandsspanning from the membrane through the interior of each cell. Thus, in astepwise fashion, any electric field imbalance (possibly because ofdielectric shielding inside the body) could be carried deep into thebody as dipoles within these nonconductive pathways. Also, ionicpolarization may occur in body fluids between the cells.

In an alternate, or possibly additional, theory of operation it may bethat the continually changing natural charge distribution on, in, andaround cells because of metabolic activities can be effected by anexternal static electric field. Although the electric field is zeroinside of a homogeneous conductive object, a non-zero field can existinside such an object if a charge is contained within a cavity in theobject. The nonconductive proteins and so forth inside the body could beconsidered to be cavities inside of an otherwise conductive object.Also, the labyrinth of nonconductive structures in the body may createdielectric shielding which would create a nonuniform, and thus non-zero,electric field inside the body which could influence natural chargedistributions on or in cells. An unnatural charge distribution on or incells, or in the Helmholtz plane around cells, would influence theirmetabolic activities, and any of the previously mentioned theoreticaleffects could come into play at that time to favor reaction with abioactive agent in the region.

Following the studies with electric fields alone, the inventor beganstudies comparing tumor growth in Control Groups of mice to that in TestGroups with a bioactive agent and a polarizing field applied. The samemethods, mice, and tumor types of the previous studies were used. Themeasurement criteria, again extrapolated from the National CancerInstitute's test protocols #3C872 and #3CDJ2, is initial tumor sizereduction. The limited treatment regimen possible with mice, and thefast growth rate of the tumor, is such that long-term regression of thetumor is not expected.

EXAMPLE C

In one study, three days after tumor implantation, the mice wereseparated into four Groups of equivalent tumor size, with the tumor sizeof each animal ranked on a scale of 1 to 5:

0.=not visible

1.=visible to under 3 mm at the longest axis

2.=3 mm to under 4.5 mm at the longest axis

3.=4.5 mm to under 6 mm at the longest axis

4.=6 mm or longer at the longest axis

5.=tumor developing the length of the implant needle track

Following this the Groups were assigned to a test method using therandom number generator of a calculator. The test method includedassigning two of the Groups for exposure to a static electric fieldduring days 3-6 of the test. All Groups were housed in identical 66quart cages with a hardware cloth floor to minimize electrostatic chargegeneration for the duration of the test, except that the two Groupsexposed to a static electric field were moved on days 3-6 to cages witha charged screen above the animals (separated from the animals with astyrene grid), a styrene grid floor, and a charge or ground plate under(outside) the cage. The distance between the top screen and outsideplate was 3½″ in both cages and the animals were maintained in thisspace without being able to touch either surface.

The treatment methods applied to the Groups were:

GROUP 1: Control Group with no bioactive agent or polarizing fieldapplied (10 animals in the Group).

GROUP 2: Treated Control Group with 12 mg/kg adriamycin (Sigma #D4035)administered by intraperitoneal (i.p.) injection, to 11 animals, once onday 3 after the tumor implant (the tumor implant was considered day 0).

GROUP 3: Test Group with 12 mg/kg adriamycin administered i.p., to 11animals, once on day 3, plus immediately following the injection theanimals were exposed to a static electric field for 72 hours (on days3-6) by maintaining the top screen at −5,000 volts DC, and bymaintaining the outside (bottom) plate at +5,000 volts DC.

GROUP 4: Test Group with 12 mg/kg adriamycin administered i.p., to 11animals, once on day 3, plus the animals were exposed to a staticelectric field for 72 hours (on days 3-6) by maintaining the top screenat −15,000 volts DC, and by grounding the outside (bottom) plate.

The treatments had time to exhibit their maximum effect by day 13, andthe following TABLE 1 shows the tumor size comparisons:

TABLE 1 GROUP 1 GROUP 2 GROUP 3 GROUP 4 Day 3 Tumor Size 5 5 5 5 4 4 5 53 3 3 4 3 3 3 4 2 2 2 2 2 2 2 2 1 1 2 2 1 1 1 1 1 1 1 1 0 0 1 1 — 0 0 02.2 mean 2.0 mean 2.3 mean 2.4 mean DAY 13 Tumor Size 2,583 mg 89 mg 385mg 14 mg 2,527 44 48 14 1,762 31 33 0 1,313 28 12 0 1,162 6 12 0 990 3 00 882 0 0 0 685 0 0 0 744 0 0 0 149 0 0 0 — 0 0 0 2,797 mg 201 mg 490 mg28 mg (1,280 mean) (18.3 mean) (44.5 mean) (2.5 mean)

In TABLE 1, the “-” in GROUP 1 indicates that this Group contained onlyten mice while the remaining Groups had eleven. The results shown inTable 1 can be summarized as follows:

GROUP 1 (untreated control) illustrated the normal aggressive growth ofthe tumor, starting with a group tumor mean of 2.2 on day 3, thengrowing to a mean of 1,280 mg on day 13. Note that one animal in GROUP 1started with a “not visible” tumor on day 3, and all mice in this grouphad visible tumors by day 13.

GROUP 2 (treated with adriamycin only) went from a group tumor mean of2.0 on day 3, to 18.3 mg on day 13. This group started with 2 “notvisible” tumor animals on day 3, and increased this to five not visibleon day 13.

GROUP 3, treated with adriamycin plus 72 hours of a static electricfield created with −5,000 volts above the animals and +5,000 volts belowthe animals, did worse than GROUP 2. GROUP 3 went from a tumor mean of2.3 on day 3 to a mean of 44.5 mg on day 13. A large contribution tothis mean came from one animal which had very large tumor growth (385mg). However, dropping this animal from the Group still indicates theGroup did no better than GROUP 2. This Group started with 1 “notvisible” tumor on day 3, and increased this to 6 not visible on day 13.The poor showing of GROUP 3 (compared to GROUP 4) may be because thetotal field strength was only 10 KV compared to 15 KV in GROUP 4.However it may also be that, in this situation, charged plates on bothsides of the animals did not create as favorable a condition forreactions with the bioactive agent as did a charged plate on one sideand ground plate on the other. For example, the static electric fieldinfluencing Group 3 from two directions at once may be too uniform, soit could rotate but not move dipoles and charges inside the animals asmuch as may have occurred inside the Group 4 animals.

GROUP 4, treated with adriamycin plus 72 hours of a static electricfield created with −15,000 volts above the animals and ground potentialbelow, showed definite improvement over the adriamycin only GROUP 2.That is GROUP 4 started with a mean tumor size of 2.4 on day 3, andincreased to only 2.5 mg on day 13 (7 times smaller than the adriamycinonly group). Also, this group started with one not visible tumor on day3 and increased it to 9 not visible on day 13.

In an additional indication that the electric field in GROUP 4 wasincreasing the adriamycin action over GROUPS 2 and 3, starting aroundday 25, it was noted that the animals in the three Test Groupsadministered adriamycin were experiencing hair loss. This is a normalreaction and is due to the fact that adriamycin destroys quicklydividing cells, such as tumor and hair follicle cells. Hair from thewaste trays under each cage was collected from days 30 to 37, and it wasfound that GROUP 2 lost 0.16 g while GROUP 4 lost 1.95 g of hair (12.2times more than the adriamycin only group), and that GROUP 3 lost 0.10 g(about the same as GROUP 2). Again this is a solid indication that thestatic electric field in GROUP 4 increased the action of the adriamycin.

EXAMPLE D

The inventor's next study confirmed that a polarizing field enhances theaction of adriamycin, and also inadvertently demonstrated that apolarizing field can increase potency of a toxic bioactive agent(adriamycin) to a lethal degree. In this study, after tumorimplantation, the mice were separated into four Groups of equivalenttumor size and placed in hardware cloth floored cages. There were elevenmice in each Group. The Groups were randomly assigned as:

GROUP 1: Treated Control with an i.p. injection of 8 mg/kg adriamycin ondays 3 and 5. No exposure to polarizing fields.

GROUP 2: Test Group with an i.p. injection of 8 mg/kg adriamycin on days3 and 5. Immediately following each injection, the animals were movedinto a cage where they were exposed for four hours to a static electricfield between a top sheet of aluminum foil (sealed between two ⅛″ thickplexiglas sheets) 1¼″ above the animals and a grounded aluminum plateunder (outside) the cage. A potential of −15,000 volts DC was applied tothe aluminum foil. The distance between the top aluminum foil and theoutside grounded plate was 3⅝″ and the animals were maintained betweenthe top foil and outside plate on a styrene grid floor. The animals weremoved back into hardware cloth floored cages after the four hourexposure.

GROUP 3: Test Group with an i.p. injection of 8 mg/kg adriamycin on days3 and 5. Immediately following each injection, the animals were moved toa cage (like that of GROUP 2) for a four hour exposure to continuingcycles of 15 minutes of −15,000 volts DC applied to the aluminum foilabove them and 15 minutes of +15,000 volts applied to the aluminum foil.The animals were moved back into hardware cloth floored cages after thefour hour exposure.

GROUP 4: Test Group with an i.p. injection of 8 mg/kg adriamycin on days3 and 5. Immediately following each injection, the north seeking pole ofa ½″ diameter by {fraction (3/16)}″ thick 10,800 gauss rare earth magnet(8 lb. holding force) was glued to each animal over the tumor site with2 small drops of #6001 Super Glue Gel (3M Company). Following this, forthe next four hours, each animal was restrained in a clear 1¼″OD by1⅛″ID by 4¾″ long plexiglas tube to prevent the animals from removingthe magnets. The plexiglas tubes were placed far enough apart to preventintermingling of the magnetic fields, and after four hours the magnetswere removed and the animals placed back in a hardware cloth flooredcage.

By day 10 (5 days after the second injection), while the tumors wererelatively small in all Groups, animals in the three Test Groups starteddying, indicating that the polarizing fields (static electric fields inthe case of GROUPS 2 and 3 and static magnetic fields in the case ofGROUP 4) had increased the potency of the normal adriamycin effect to alevel beyond tolerance by the bodies of the mice. Also, the animals withthe smallest tumors died first, indicating enhanced adriamycin action onboth the tumors and the bodies of these animals. The following TABLE 2shows the mortality dates of animals in the Test Groups, compared to theControl Group, over the 30 day study.

TABLE 2 Mortality Days GROUP 1 GROUP 2 GROUP 3 GROUP 4 Day 0. ImplantTumors In All Groups 1. 2. 3. First Injection All Groups 4. 5. SecondInjection All Groups 6. 7. 8. 9. 10. XXX 11. X X 12. XXX XXXXXX XX 13. X14. 15. 16. 17. 18. X 19. X 20. 21. 22. X XX 23. 24. 25. X 26. 27. X 28.X 29. 30. X

The results shown in TABLE 2 can be summarized as follows:

GROUP 1 (treated with adriamycin only) had one animal die at day 30, andthis was from the effect of the tumor, not the adriamycin. By this timethe tumors had developed to an average weight in this group of 12% ofthe animals' total body weight.

GROUP 2 (adriamycin plus a static electric field due to −15,000 volts DCon the top foil) lost half of it's animals by day 22 and all of thesedeaths could be attributed to the increased potency of the adriamycinsince the average tumor weight in the group was only about 2% of theaverage body weight at this time. Only four live animals remained inthis group at day 30, and their average tumor weight was 1,189 mgcompared to 2,357 mg for Control Group 1.

GROUP 3 (adriamycin plus 15 minute cycles of 15 minute negative thenpositive 15,000 volt DC fields) lost half of it's animals by day 12 andall of these deaths could be attributed to the increased potency of theadriamycin since the average tumor weight in the group was less than 2%of the average body weight at this time. Only four live animals remainedin this group at day 30, and their average tumor weight was 1,400 mgcompared to 2,357 mg for Control Group 1.

GROUP 4 (adriamycin plus a static magnetic field) lost half of it'sanimals by day 12 and all of these deaths could be attributed to theincreased potency of the adriamycin since the average tumor weight inthis group was only about 0.6% of the average body weight at this time.All of the animals in this group had died by day 30.

Examinations of the first 50% of animals to die in each Test Groupshowed kidney and possible liver damage. This would be expected becauseadriamycin is known to normally concentrate in both. Also, thereappeared to be heart enlargement in many of the Test Group animals, andirreversible myocardial toxicity with delayed congestive heart failureis a sign of adriamycin overdose. Like all drugs, particularlychemotherapeutic agents, adriamycin will kill the body above a certaindose potency level. In this study, the same dose level was given to allanimals, and was tolerated by the treated control group. But the variouspolarizing fields the Test Groups were exposed to increased the potencyof the dose to a lethal level, even though the fields were only appliedfor four hours after administering the chemotherapeutic agent.

Observing the same effect from both static electric and static magneticfields supports the conclusion that both types of field influence normalorientation and distribution of, and possibly movement of, charges andproteins in the body. It also supports the conclusion that both types offield accelerate cancer growth (most likely by influencing the normalorientation and distribution of, and possibly movement of, charges andproteins in the body) and that the cancer cells consequently, eitheringest more adriamycin than they otherwise would or become moresusceptible to adriamycin poisoning.

In this study the static magnetic fields appeared to have a strongereffect than the static electric fields. Magnetic fields are known topenetrate tissue almost unimpeded, and this may account for the studyfindings. However, in this study, the magnetic force field would alsohave been much stronger than the static electric field applied, bothbecause the magnets were very strong, and because the magnets were veryclose to each animal whereas the aluminum foil connected to the powersupply was over 1″ away. Also, without a second plate for the magneticfields to connect with, the magnetic fields would have been even morenonuniform than that of the electric fields.

The inventor believes the applied static magnetic fields in this Studywould operate in a different manner than the static electric fields, butthe ultimate results may be the same. Static magnetic fields easilypenetrate tissue, but they do not influence electric charges unless thecharges move in relation to the magnetic field (or unless the fieldmoves in relation to the charges). The metabolism of the body constantlymoves, separates, or combines electric charges (polar molecules) in andaround the countless proteins and lipids we are made of. The appliedmagnetic field may have oriented and influenced these naturally movingcharges to move in an unnatural direction. This would have caused aseparation and aggregation of these charges over time. Each of thesecharges has a static electric field of its own, and the combined staticelectric field influence of this unnatural grouping of charges at thecellular level could result in any of the above noted actions beingpossible because of externally applied static electric fields.

Also in this study, the polarizing fields were affecting all of eachanimal's body, and thus increasing the action of the adriamycin in allparts of the body. This is true for even the magnetic fields; themagnets were placed in one location but their force field linesconnected from the north pole to the south pole and this path wouldengulf the entire animal, which was only about 2½″ long. In humanpatients, it would be possible, and most often desirable, to confine thepolarizing field effect to only a select body region for maximumtherapeutic effect in that region while sparing the rest of the bodyfrom the increased effect.

EXAMPLE E

In the inventor's next study, after tumor implant, the mice wereseparated into four groups of equivalent tumor size and randomlyassigned as:

Group 1: (10 animals) Treated Control with i.p. injection of 12 mg/kgadriamycin on day 4. No exposure to polarizing fields.

Group 2: (11 animals) Test Group with an i.p. injection of 12 mg/kgadriamycin on day 4, then 10 days exposure to a 15,000 volt staticelectric field in a cage with a plastic grid floor, a charged top plateof screen wire sealed between two ⅛″ thick sheets of plexiglas, and agrounded wire grid under the cage 3½″ from the charged top plate(animals could not touch the ground or charged screen). The charge onthe top plate screen wire was continuously cycled each 15 minutesbetween positive 15,000 volts and negative 15,000 volts.

Group 3: (11 animals) Test Group with an i.p. injection of 12 mg/kgadriamycin on day 4, then 10 days exposure to a 15,000 volt staticelectric field in a cage with a grounded wire grid floor and a chargedtop plate of screen wire sealed between two ⅛″ thick sheets of plexiglas4½″ from the floor (approximately 3½″ from the animal's back to thecharged screen). The animals were touching the grounded floor, but couldnot touch the charged screen. The charge was continuously cycled each 15minutes between positive and negative 15,000 volts.

Group 4: (11 animals) Test Group with an i.p. injection of 12 mg/kgadriamycin on day 4, then 10 days exposure to a 15,000 volt staticelectric field in a cage with a plastic grid floor, a charged top plateof screen wire sealed between two ⅛″ thick plexiglas sheets, and nonearby ground surface (the nearest ground was a concrete floor 4′3″away). The charge was continuously cycled each 15 minutes betweenpositive and negative 15,000 volts.

At three different times during the study, a Leeds and Northrup 0.1sensitivity microampere meter was used to measure any current flow toground in the Group 2 and 3 cages (only groups with a nearby ground). Nocurrent flow was detected for either Group.

Tumor weight was measured and averaged for each Group starting at thetime of injection and field exposure (Day 4), then on days 8, 11, and14. Table 4 shows the percentage of tumor weigh loss (regression) orgain for each Group from day 4:

TABLE 4 DAY 8 Day 11 Day 14 Group 1: −26% −3% +110% Group 2: −79% −81%−86% Group 3: −68% −78% −64% Group 4: −72% −75% −51%

The three static electric field exposed Groups did considerably betterthan the adriamycin only Group, with the mean tumor weight of the fieldexposed Groups more than three times smaller than the adriamycin onlyGroup by day 14. A Statistical analysis of the results, using bothnon-parametric and parametric methods, was also conducted for eachmeasurement day. There was no statistically significant difference inthe tumor sizes of any of the Groups on day 4. The three field exposedGroups demonstrated significant tumor regression over the adriamycinonly Group on all three days, with probability values as low as 0.001.Also, the odds that an animal treated with field exposure would dobetter than an adriamycin only treated animal were as high as 8.3 to 1.

EXAMPLE F

In the inventor's next study, tumor bearing mice in four groups werefirst injected with 10 mg/kg adriamycin then each group was alternatelyplaced in wire grid floor cages for rest, and 1¼″ OD×⅞″ ID×3½″ longclear polycarbonate restraining tubes for exposure to polarizing fields(the animals in the Treated Control Group 1 were placed in the same typeof tubes, but polarizing fields were not applied). The restraining tubesfor all animals were placed on special holders during each fieldexposure period, with a polarizing field element placed next to eachtumor (on the outside of the tube) for the Group 2, 3, and 4 animals (nofield element was used for the Group 1 animals). All restraining tubeswere placed far enough apart to minimize interaction of the variouspolarizing fields used during each exposure period. The schedule for allgroups in and out of the cages and restraining tubes was:

4 hours in restraining tubes,

9 hours in cages,

8 hours in restraining tubes,

8 hours in cages,

8 hours in restraining tubes,

12 hours in cages,

8 hours in restraining tubes,

7 hours in cages,

8 hours in restraining tubes,

the remainder of the 20 day study in cages.

Seven days after tumor implant, the inventor separated the mice intofour groups of equivalent tumor size and randomly assigned the groupsas:

Group 1: (10 animals) Treated Control with an i.p. injection of 10 mg/kgadriamycin on day seven. No exposure to polarizing fields.

Group 2: (11 animals) Test group with an i.p. injection of 10 mg/kgadriamycin on day seven, then exposure to a cycling 15,000 volt staticelectric field emanating from a ¼″ brass ball maintained next to eachanimal's tumor (ball outside of the restraining tube). Each brass ballin this group was connected to a DC power supply in which the outputchanged from positive 15,000 volts to negative 15,000 volts each 5seconds throughout each field exposure period.

Group 3: (11 animals) Test group with an i.p. injection of 10 mg/kgadriamycin on day seven, then exposure to a constant 15,000 volt staticelectric field emanating from a ¼″ brass ball maintained next to eachanimal's tumor (ball outside the restraining tube). Each brass ball inthis group was connected to a negative 15,000 volt DC power supplythroughout each field exposure period.

Group 4: (12 animals) Test group with an i.p. injection of 10 mg/kgadriamycin on day seven, then exposure to the north-seeking pole of a10,800 gauss static magnetic field emanating from ½″ diameter by{fraction (3/16)}″ thick rare earth magnet maintained next to eachanimal's tumor (magnet outside the restraining tube) throughout eachfield exposure period.

Tumor weight was measured and averaged for each Group starting at thetime of injection and field exposure (day 7), then on days 11, 14, 17,and 20.

TABLE 5 shows the percentage of each Group's mean tumor weight loss(regression) or gain from day 7, with the numbers in parentheses showingthe Group median tumor weight loss or gain percentage from day 7.

TABLE 5 G1 G2 G3 G4 Day +14% (+29) −46% (−18) −53% (−42) −70% (−71) 11Day +24 (+33) −40 (−36) −58 (−55) −70 (−76) 14 Day +225 (+75) +59 (+77)+35 (+25) −34 (−42) 17 Day +1,110 (+910) +807 (+940) +596 (+547) +272(+64) 20

Again, as with the previous studies, the polarizing field-exposed Groupsdid remarkably better than the adriamycin only Group.

Group 1, the adriamycin only group did not achieve mean or median tumorsize reduction at any measured point in the study. The inventor believesthe normal tumor growth rate was simply slowed by the adriamycin.

Group 2, exposed to 5 second cycles of positive then negative 15,000volts, achieved statistically significant tumor regression through day14, but not as much as Group 3. The inventor's previous studies haveshown 15 minute cycles of positive then negative cycles 15,000 voltscreating more enhancement of the adriamycin than a constant (samepolarity) charge. The 5 second cycle time in this study then appears tobe approaching the lower (shorter) cycle time for efficacy, and theinventor feels changing the polarity or strength of the polarizingfields in times less than 1 second would have very little efficacy.

Group 3, exposed to a constant negative 15,000 volt field, achievedstatistically significant tumor regression through day 17. Thus thisgroup demonstrated the strongest adriamycin enhancement of the twoelectric field exposed groups.

Group 4, exposed to a 10,800 gauss static magnetic field, achievedstatistically significant tumor regression lasting throughout the 20 daystudy. The inventor's previous studies have shown that this magneticfield can provide adriamycin enhancement at a higher level than a 15,000volt static electric field.

A statistical analysis of the probable significance of the differencesin tumor weight loss/gain of the polarizing field exposed groups,compared to the adriamycin-only Group 1, was conducted using aKruskal-Wallis analysis of variance followed by Mann-Whitney tests ofthe pairwise differences between Groups 2, 3, and 4 with Group 1. Also,the resulting U statistic was transformed into the odds that an animaltreated in the manner of 2, or 3, or 4, would have more of a decrease(or less of an increase) in tumor weight than an animal treated withadriamycin only. TABLE 6 shows the probability values for each day, withthe odds shown in parentheses (4 to 1 odds that an animal in Group 2would do better than an animal in Group 1 is the first figure forexample). There was no statistically significant difference in the tumorsizes of any of the Groups on day 7 (p=0.181).

TABLE 6 Group 2 Group 3 Group 4 Day 11 p = 0.0166 (4) p = 0.0038 (7) p =0.0001 (39) Day 14 0.0038 (9) 0.0015 (10) 0.0001 (119) Day 17 0.0783 (3)0.0091 (5) 0.0015 (9) Day 20 0.7247 (1) 0.1809 (2) 0.0295 (3)

Adriamycin is known to degrade quickly in the body environment, withcleavage of the glycosidic group and changes in the 4-hydroxy groupbreaking the material down into less effective metabolites which arequite different than adriamycin. The alpha phase half-life isapproximately 1 hour, and the beta phase half-life can run 21 to 48hours. Beyond this, a detectable level of the metabolites may persist inthe serum for over a week. Without question, both the static electricand static magnetic fields successfully enhanced the action of bothadriamycin and its metabolites against the tumors.

In total, the inventor's studies demonstrate that static electric andstatic magnetic fields can increase the potency and efficacy ofbioactive agents on the body. The fact that these fields exhibit aninfluence on tumors without a chemotherapeutic agent applied, and alsoexhibit influence on cells other than tumors, such as hair, kidney,liver, and heart cells, indicates that the invention will be useful withother types of bioactive agents and diseases. For treatment purposes,the power, application method, and time of application of the polarizingelectric and/or magnetic fields in a specific treatment will depend uponfactors such as, for example, the bioactive agent used, the type andlocation of the malady or disease, and the treatment goal. In most casesa preferred bioactive agent for treatment of a specific disease will beknown, and the desirability of the bioactive agent/polarizing fieldcombination can be determined with standard protocols and animal modelsof the disease, typically using an escalating dose level, such as amodified Fibonacci series, for example.

The benefits from the invention could be tremendous. For many maladies,a few percent increase in efficacy of the bioactive agent used can makethe difference in whether treatment is successful or not. Consider thefollowing highly simplified example with cancer:

Depending on the tumor type and it's location, cancer cells can divide(or double) in time frames ranging from less than 24 hours to numbers ofdays. Assume a cancer patient has 100 cancer cells which normally doubleeach 7 days. Typically, a patient's body cannot withstand powerfulchemotherapy treatments on more than a monthly basis. If, during weekone, the patient undergoes a chemotherapy treatment which kills 85% ofthe cancer cells, 15 viable cells would remain (day 7). During week twothe 15 cells would double into 30, then week three 60, then week four120. By the start of week five, and time for the second chemotherapytreatment, the patient would have 20 more cancer cells than before thefirst treatment, and would be losing the battle against exponential cellgrowth.

Consider the outcome of this example if the invention were used toincrease the effectiveness of the treatment by just 6%, killing 90cancer cells instead of 85. Again, the patient would start with 100cancer cells. The first chemotherapy treatment would reduce this to 10on day seven, and they would then double to 20 cells at week two, 40cells at week three, and 80 cells at week four. By the start of weekfive and time for the second chemotherapy treatment, the patient wouldhave 20 fewer cancer cells and would be winning the battle.

It is anticipated that the invention can be used in any method in whichincreasing the action of a bioactive agent would be desirable. Theoptimum treatment will in most cases depend on a number of factors suchas the bioactive agent, the response desired, and the body locationtargeted for treatment, for example. Examples of treatment methods inaccordance with the invention, for both static electric and staticmagnetic fields, include:

1. Exposing all, or some select portion, of the body to a nonuniform, orto a relatively uniform, polarizing field during a period while adesired bioactive agent is present in or on the body.

2. Exposing all, or some select portion, of the body to a nonuniform, ora relatively uniform, polarizing field during a period while a desiredbioactive agent is present in or on the body, in a manner where thepolarizing force of the field is of one polarity for a period of time ofat least one or more seconds, then changing the polarity for anotherperiod of time of at least one or more seconds. Cycling the polarity inthis manner will be done in periods long enough to allow increasedefficacy of the bioactive agent to occur, yet in periods short enough toavoid Coulomb blockade, in which charges accumulate, over time, underthe influence of the field in great enough numbers to block part of theeffect of the field. Also, occasionally changing the polarity can beused to maximize the possibility of creating a cellular condition whichfavors reaction with the applied bioactive agent. For example, it isanticipated that a static electric field may be able to rotate and/ormove molecules, in or on the cell membrane. Such movement would occurvery slowly, and specific locations of the molecule along the movementpath may favor reaction with the applied bioactive agent due to thecombined effect of the charge distribution on the molecule and onneighboring sites the moving molecule passes by. The moving moleculewould eventually reach a point where it could no longer move in responsethe polarizing field, and this would reduce some of the extra chance ofcreating a condition favoring reaction with the bioactive agent.Reversing the field polarity (or changing the location of the fieldemanating source) would then place the molecule under the influence of aforce with a different vector direction, again moving the molecule andmaximizing opportunities to create conditions favoring reaction with thebioactive agent.

3. Exposing all, or some select portion, of the body to a nonuniform, ora relatively uniform, polarizing field during a period while a desiredbioactive agent is present in or on the body, in a manner where thestrength (amplitude) of the field is increased and/or decreased overtime. Increasing and/or decreasing the strength of the field in thismanner would allow different degrees of cellular actions to occur ateach field strength level and thus insure that reaction with thebioactive agent will occur even if only one specific level of fieldstrength favors the reaction.

4. Exposing all, or some select portion of, the body to a nonuniform, ora relatively uniform, polarizing field during a period while a bioactiveagent is present in or on the body, in a manner where the fieldapproaches the body from one or more directions for a period of time,then changes to one or more additional or different directions foranother period of time. The periods of time may be equal or different.This method helps avoid Coulomb blockade, and also exposes the targettissue region, and ultimately each cell, to a polarizing force fromdifferent directions to ensure that cellular reaction with the bioactiveagent will occur even if only one of the directions favors the reaction.This method may also move molecules or charges along a travel path whichmaximizes opportunities (as noted in #2 above) to create conditionsfavoring reaction with the bioactive agent.

5. Any combinations of the above methods may be used to meet specificneeds.

The attached drawings show a few examples of basic embodiments andmethods of use to aid in understanding the invention.

FIG. 1 shows a preferred embodiment for exposing all, or a largeportion, of a patient's body to the influence of a polarizing field(here a static electric field). The patient 1 is placed on a treatmentelement, shown in this example as treatment pad 2, which contains aconductive element (not shown in FIG. 1) covered and insulated fromcontact with the patient's body. A terminal 3 is connected to theconductive element in the treatment pad 2, and the patient is exposed toa nonuniform static electric field during the period that a power supply(not shown in FIG. 1) is applied to the conductive element via theterminal 3 so as to maintain a charge on the conductive element. Thefield strength and/or polarity may be periodically changed during thetreatment if desired.

If desired for a particular treatment method, an additional conductiveelement 4 may be positioned above the patient. A terminal 5 is providedto permit the conductive element 4 to be connected to ground, or to apower supply. Grounding conductive element 4 will provide a relativelyuniform static electric field between treatment pad 2 and conductiveelement 4 to which the patient is exposed. Supplying conductive element4 with a voltage having a different polarity from that supplied totreatment pad 2 will also provide a relatively uniform static electricfield between treatment pad 2 and conductive element 4. Supplyingconductive element 4 with a voltage having the same polarity as thatsupplied to treatment pad 2 will provide a nonuniform polarizing forcefield between treatment pad 2 and conductive element 4.

In an example of an alternate use, to meet specific needs, conductiveelement 4 may be periodically charged alone by the power supply, orcharged while the conductive element in treatment pad 2 is grounded, tohave the static electric field approach the patient from a differentdirection than treatment pad 2.

In still another alternate use example, the field strength and/orpolarity emanating from treatment pad 2 and/or conductive element 4 maybe periodically changed during the treatment if desired.

Also, treatment element 2 may contain more than one conductive element,with the conductive elements insulated one from another, and a staticelectric charge may be alternately applied to the different conductiveelements to have the polarizing field approach the patient fromdifferent locations. In this same regard, different strengths orpolarities of charge may be applied to the different conductive elementsto control the power and direction of the polarizing field reaching thepatient's body.

As an alternative to laying the patient directly on treatment pad 2, thepatient may be laid on a nonconductive surface, and the chargedconductive element may be placed at some other location under (or evenabove) the patient. This method would also accommodate placing thecharged conductive element at an angle to, instead of parallel with, thepatient's body to expose the patient to a nonuniform static electricfield which also has different gradients which may enhance movement ofmolecules and charges within the patients body to achieve a chargedistribution favoring reaction with the bioactive agent. Otherplacements of treatment pad 2 and conductive element 4 may also be usedto create field gradients, such as placing treatment pad 2 parallel tothe patient and conductive element 4 at an angle to treatment pad 2 forexample.

Also, it will sometimes be desirable that treatment pad 2 and conductiveelement 4 be of different size. For example, if conductive element 4 issmaller than treatment pad 2, more nonuniform fields are created betweentreatment pad 2 and conductive element 4 around the edges of conductiveelement 4, and conductive element 4 can be positioned to have these morenonuniform fields interact with the target regions of the patient'sbody.

FIG. 2 is a cutaway portion of an example of a suitable structure for atreatment element such as treatment pad 2 in FIG. 1. Thepreviously-mentioned conductive element is identified by referencenumber 6 in FIG. 2 and is sandwiched between two insulating covers 7 and8. The conductive element 6 may be any electrically conductivesubstance, however flexible substances such as silver coated fabric(Monsanto Metallized Materials, St. Louis, Mo. for example) or wirecloth (Tetko, Inc., Briarcliff Manor, N.Y. for example) are preferred.The insulating covers 7 and 8 may be any electrically insulatingsubstance, however puncture resistant flexible substances, such as nylonlaminates for example, which can be heat sealed at 9 around the edges toencase the conductive element 6, are preferred. Allied Corporation,Morristown, N.J. and Printpack, Inc. Grand Prairie, Tex. are examples ofsuppliers of such nylon materials. The insulating cover must be thickenough to prevent the electrical charge chosen for the conductiveelement 6 from arcing through the insulating cover if the patientinadvertently touches a ground, or opposite potential, while theconductive element 6 is charged. For example, Allied's nylon-6 film hasa dielectric strength of about 700 volts/mil, and a safety factor mustbe included. A 1000% safety factor, for example, would reduce this to 70volts/mil, and if the conductive element 6 is intended to carry 5,000volts, the insulating cover 7 over the conductive element 6 would needto be at least 0.071″ thick. Fabrics or other surfaces such as blankets,etc., may be placed on top of the insulating cover 7 for patientcomfort, and also the treatment pad will conform to the patient's bodyif it is placed on top of an insulated mattress, etc.

The additional conductive element 4 of FIG. 1 may be constructed in thesame manner as shown in FIG. 2, and this additional conductive elementmay be laid directly on top of the patient. However, more control overthe static electric field is achieved (as the patient moves around,etc.) by suspending the conductive element 4 above the patient from aninsulated stand. In this situation it is preferable that conductiveelement 4 be rigid, and a convenient way to accomplish this is to userigid material, such as acrylic sheet (Rohm & Haas Company,Philadelphia, Pa.) for example, as the insulating covers 7 and 8, and toseal around the edges at 9 with RTV silicone or other materials toencase the conductive element. Acrylic has a dielectric strength around350 volts/mil, and again the required thickness of insulating covers 7and 8 would depend on the maximum voltage they are expected to besubjected to.

FIG. 3 shows an example of a power supply system used for placing chargeon the conductive element 6 in FIG. 2 from an output 13. The powersupply 10 for charging the element 6 may be as simple as anelectrostatic charge generator, such as a Wimshurst or Van de Graaffgenerator for example. Or alternately, the treatment element maycomprise a self-contained electret. However, well controlled andregulated high-voltage DC power supplies are widely available andgenerally preferred because the voltage is easily maintained andcontrolled. Spellman High Voltage, Plainview, N.Y. and American HighVoltage, Alpine, Calif. are examples of suppliers offering high voltageDC power supplies with adjustable outputs ranging from 100 to as much as100,000 volts in either negative or positive potential, or both. Thesesupplies may be specified with current limiting circuits which shut downthe supply if a specific current level is exceeded, and thus minimizedanger to the patient in case of a short circuit, etc. Maintaining thestatic electric field requires almost no current flow, only enough tobring element 6 to a desired charge level and then maintain that level.A current limiting resister 11, such as a high-voltage resistor fromCesiwid, Inc., Niagara Falls, N.Y. for example, typically with aresistance around 1 megohm to 20 megohms depending on the power supplyvoltage, is preferably placed in the circuit as an additional safetymeasure for the patient. A single pole-double throw high-voltage relay12, available from Kilovac Corp., Santa Barbara, Calif. for example, orother switching technique, is optional and shown as a convenient methodof changing the charge from one location to another, such as fromtreatment pad 2 below the patient to the additional conductive element 4above the patient, for example. For this purpose, a relay terminal 14 isconnected to the terminal 3 of the treatment pad 2 and a relay terminal15 is connected to the terminal 5 of the conductive element 4. A timer(timer and relay coil not shown) periodically energizes the relay coilto control the time that the charge is maintained at each location. Thiswould expose the patient to a nonuniform static electric fieldalternately approaching the body from different directions to ensurethat cellular reactions occur with the bioactive agent even if thereaction favors only one direction at a certain point in time. Thiswould also minimize Coulomb blockade, and dielectric shielding.

As an additional option, an output voltage programmer 16, such as aDigital to Analog converter and a suitably programmed computer (Datel,Inc. Mansfield, Ma., for example) may be used to slowly increase ordecrease the voltage of any of the outputs (by driving the standardremote voltage control circuit of the supply) to ensure that the desiredcellular reaction with the bioactive agent occurs even if only one rangeof voltage levels favors the reaction at a certain point in time.

FIG. 4 shows a power supply system which utilizes a double pole-doublethrow relay 17 as a convenient way of periodically changing a ground anda charge potential between two locations, such as between the treatmentpad 2 below the patient and the additional conductive element 4 abovethe patient for example, by way of terminals 18 and 19. This wouldexpose the patient to a relatively more uniform static electric fieldwith its field alternately approaching the patient in differentdirections to ensure that cellular reactions with the bioactive agentoccur even if only one direction favors the reaction at a certain pointin time. This would also minimize Coulomb blockade. A timer (timer andrelay coil not shown) periodically energizes the relay 17 to control thedesired time of the field from one direction.

In an additional use of the power supply system of FIG. 4, the lowercontact of relay 17 may be disconnected from terminal 19. In thisconfiguration, when relay 17 is not activated, the voltage from thepower supply 10 would be applied to terminal 18 but ground would not beapplied to terminal 19. When relay 17 is activated, the voltage would beapplied to terminal 19 and ground would be applied to terminal 18. If,for example, terminal 18 is connected to the terminal 5 of theadditional conductive element 4 above the patient and terminal 19 isconnected to the terminal 3 of the treatment pad 2 below the patient,this relay configuration would allow a nonuniform polarizing force fieldto be applied to the patient while the coil of relay 17 is notactivated, and then a relatively more uniform field to be applied whilethe coil of relay 17 is activated. This situation would first allow thenonuniform field to maximize bioactive agent reactions possible withthat type of field for some period, then a periodic change to arelatively more uniform field would allow bioactive agent reactionsfavoring that type of field to occur for some period.

FIG. 5 shows an example of a further power supply system using powersupplies 20 and 21 of different polarity to provide positive andnegative voltages to two different locations from terminals 22 and 23.An example of this use would be applying a negative potential fromterminal 22 to the additional conductive element 4 in FIG. 1, and apositive potential from terminal 23 to the treatment pad 2 in FIG. 1, toexpose the patient to a strong, relatively uniform, static electricfield without requiring an excessively high voltage on either thetreatment pad 2 or the conductive element 4. In an optional use, adouble pole-double throw relay 24 having terminals 25 and 26 may be usedto periodically change the charge polarity between two locations, suchas treatment pad 2 and conductive element 4 in FIG. 1 for example, tominimize Coulomb blockade and also ensure that cellular reactions withthe bioactive agent will occur even if only one of the polaritylocations favors the reactions at some point in time.

Also, in another use of the power supply system of FIG. 5, only onetreatment pad, such as treatment pad 2 in FIG. 1 for example, may beconnected to either terminal 25 or 26 of relay 24, and the polarity ofthe voltage applied to the treatment pad will be reversed each timerelay 24 switches position. A timer periodically energizes the relaycoil (timer and relay coil not shown) to control the desired time bothpolarities are maintained at their respective locations. This exposesthe patient to a nonuniform field from one location, but with thepolarity reversed each time relay 24 is switched. This maximizesopportunities for creating conditions favoring reaction with thebioactive agent even if the reaction favors only one polarity atdifferent points in time. Also, this minimizes any effects of Coulombblockade. The additional conductive element 4 may be provided andgrounded if a relatively uniform force is desired for a specifictreatment.

It is noted that solid state switching may be used in place of therelays of FIGS. 3-5 if the required treatment voltage is low enough tobe handled by semiconductors. In addition, multiple power supplies maybe used, instead of the high-voltage relays of FIGS. 3-5, to applydesired voltages to treatment pads at various locations, with the timingof the voltage application to each location being controlled byswitching the power supplies on and off. Also, other output and timingoptions are possible to provide optimum action of the invention withspecific bioactive agents or treatment needs.

FIG. 6 shows a preferred embodiment of a method of applying an electricfield to only a target region of the body. This would most often be apreferred use of the invention, and would increase the potency of theadministered bioactive agent in only the target region while sparing therest of the body from the effect of the increased potency. A treatmentelement, shown here as treatment pad 27, is positioned on (adhered to,etc.) a body target region. Treatment pad 27 contains a conductiveelement which is encased in insulating material, and has a terminal 28so a desired electric charge may be applied to the conductive element. Aproperly sized version of the treatment pad construction shown in FIG. 2would serve well as treatment pad 27. Terminal 28 to the conductiveelement may be connected to any output of the power supply systems shownin FIGS. 3-5, or to other desired power systems, to apply the desiredtype of nonuniform polarizing force field to the body target region. Asan option, an additional treatment pad 29, containing an insulatedconductive element and a terminal 30 connected to the conductiveelement, may be applied to the body region, and be grounded, or receiveoutput from any of the power systems shown in FIGS. 3-5, or otherdesired power systems. Such an option may be used to provide arelatively uniform, or nonuniform, static electric field betweentreatment pads 27 and 29, and/or help direct the action of the staticelectric field through specific tissue areas.

It is noted that power supply systems for use with the invention may beconstructed small enough to comfortably wear on a belt, etc., and theinsulated treatment elements, may be maintained in place on the patientfor long-term treatment as the patient moves about.

FIG. 7 shows a preferred embodiment of a method of applying theinvention to an internal target body region (in this case the stomach)by inserting a fully insulated conductive element 31 into any bodycavity so as to bring it as close as possible to the target region formaximum effect, and also to aid in confining the effect to only thetarget region. Conductive element 31 may be of any desired shape to aidinsertion into the body cavity, and also to help expose the targetregion to the static electric field. Terminal 32 may be connected toelement 31 by shielded cable to isolate the field from undesired bodyareas. Terminal 32 may be connected to any desired power system to applythe desired type of static electric field to the body target region. Asan option, one or more treatment pads 33, containing an insulatedconductive element connected to a terminal 34, may be appliedexternally. The treatment pad or pads 33 may be grounded, or receiveinput from a power supply system, to provide a relatively uniform, ornonuniform, static electric field between the conductive element 31 andthe treatment pad or pads 33, and/or help direct the action of thestatic electric field through specific tissue regions. In some cases, itmay be desirable to surgically implant the conductive element 31 into atarget region of the patient's body, or to place conductive element 31in a desired internal body location with minimally invasive techniques,such as catheter or laparoscopic techniques for example. Also, thepreviously discussed alternative methods of changing polarity, strength,etc., on or between conductive element 31 and terminal 34 may beadvantageously used.

The above examples illustrate basic methods of applying a nonuniform, ora relatively uniform, static electric field, to various patient bodylocations. In all of these examples, the properties of the electricfield influencing the patient may be selectively controlled or changedin many ways. As a few examples, the electric field may be:

1. Maintained at a desired field strength level throughout thetreatment.

2. Periodically changed from one field strength level to one or moreother field strength levels throughout, or changed at any time during,the treatment.

3. Applied for only desired time periods throughout the treatment.

4. Periodically changed from one vector direction, to one or more othervector directions, throughout, or changed at any time during, thetreatment.

5. Periodically changed from one polarity to another polaritythroughout, or at any time, during the treatment.

6. Periodically applied as a nonuniform field, then as a relatively moreuniform field, throughout, or changed at any time during, the treatment.

7. Changed to any combinations of the above at desired time periodsthroughout the treatment.

FIG. 8 shows an embodiment of a method for exposing all, or largeportions, of a patient's body to the influence of a magnetic fieldproduced by permanent magnets. The patient 1 is placed on a treatmentelement, shown here as treatment pad 35, which contains a plurality ofpermanently magnetized elements. The magnetized elements areconveniently embedded or maintained in a preferably soft structureproviding comfort for the patient. Depending on the field strength andthe depth of tissue penetration desired, as well as the direction of themagnetic field vector desired in a particular treatment, the poles ofthe individual magnetized elements in a particular treatment pad may beplaced in an alternating north then south seeking pole arrangement, orin an arrangement with all north and all south poles pointing in thesame direction. The poles of the magnetized elements are preferablepositioned to face the patient's body, and the magnetic fieldcontribution from each element penetrates the body as the individualfields of the magnetized elements curve (depending on the polearrangement) toward, or away from, the poles of the adjacent elements.

If desired for a particular treatment method, an additional treatmentelement, shown here as structure 36, with a plurality of permanentlymagnetized elements may be positioned on or above the patient. Themagnetized elements in this structure may be imbedded in soft materialfor patient comfort, and also to conform to the patient's body if thestructure is to be laid on the body, or the structure may hold themagnetized elements in rigid relationship if the structure is suspendedabove the patient. The poles of the magnetized elements in structure 36are preferably positioned to face the poles of the magnetized elementsin treatment pad 35, and depending on the pole arrangement desired for aparticular treatment, the patient's body would be penetrated by arelatively uniform static magnetic field (for example if the polesfacing the patient in treatment pad 35 are all north seeking, and thepoles facing the patient in structure 36 are all south seeking), or anonuniform static magnetic field (for example if the poles facing thepatient in both treatment pad 35 and structure 36 are all northseeking). In either case, the strength of the static magnetic fieldwithin the patient's body may be adjusted to a desired level by choosingmagnetized elements of specific power, or by adjusting the space betweentreatment pad 35 and structure 36. Also, the strength of the magneticfield within the patient's body may be adjusted by adjusting theposition of the patient's body in relationship to treatment pad 35 andstructure 36. For example, the patient could be laid on a table, etc.,which does not impede the passage of magnetic fields, and structure 35could be spaced some distance under the table to reduce the magneticfield strength applied to the patient.

Alternatively, structure 36 may contain magnetizable elements instead ofmagnetized elements.

Additionally, if treatment pad 35 is used without structure 36,treatment pad 35 may be placed at an angle to, instead of parallel with,the patient. Also, if both treatment pad 35 and structure 36 are used,either one or both may be placed at an angle to, instead of parallelwith, the patient.

FIG. 9 shows a cutaway portion of a treatment pad, such as 35 in FIG. 8,where the magnetized elements 37 are imbedded in a soft material 38 tomaintain the relative positions of the magnetized elements and also toprovide patient comfort (material 38 may alternately be rigid). Elements37 may conveniently be permanent magnets such as those supplied byBunting Magnetics Company, Newton, Kans. for example. The soft imbeddingmaterial 38 may be silicone rubber such as that supplied by GESilicones, Waterford, N.Y. for example. FIG. 9 shows the magneticelements 37 placed with all north seeking poles facing one direction,and all south seeking poles facing in the opposite direction. In thisarrangement, except for around the edges of material 38, the individualmagnetic field 39 emanating from the pole of each element 37 repel theindividual fields from the poles of adjacent magnetic elements. Theindividual fields thus do not traverse a short path to terminate on theadjacent magnetic elements, and would create a uniform overall magneticfield penetrating deeply, or completely through, the patient's bodydepending on the magnetization level of elements 37 and the distancebetween the elements 37 and the patient's body.

It is noted that permanent magnets may be formed by molding particles ofmagnetizable material in a desired size and shape, then the moldedmember or a specific portion of it is magnetized. Permanent magnets maythus be produced with large pole surfaces capable of exposing largeareas of the patient's body to a magnetic field from only one or twomagnets, and could be used in place of the structure of FIG. 9. Also,magnetizable particles may be calendered into flexible sheets and thenmagnetized, and such magnetized flexible sheets may be used in place ofthe structure of FIG. 9 if the lower magnetic field strength produced bysuch sheets is sufficient for the desired treatment need.

Fabrics or other surfaces such as blankets, etc., may be placed betweenthe soft material 38 and the patient for comfort, and also soft material38 will conform to the patient's body if it is placed on top of amattress, etc. The additional magnetic field structure 36 of FIG. 8 maybe constructed in the same manner as shown in FIG. 9, and structure 36may be laid directly on top of the patient. However, more control overthe applied magnetic field is achieved (as the patient moves around,etc.) by suspending structure 36 at some desired distance above thepatient, and in this instance the magnetic elements 37 may be imbeddedin, or attached to, rigid material such as epoxy for example.

FIG. 10 shows a cutaway portion of a treatment pad such as pad 35 inFIG. 8, where the magnetized elements 40 are imbedded in a soft material41 to maintain the relative position of the magnetized elements and alsoprovide patient comfort (material 41 may alternately be rigid).Magnetized elements 40 may conveniently be permanent magnets, and thesoft imbedding material 41 may be silicone rubber. FIG. 10 shows thepoles of magnetic elements 40 placed in an alternating north/southseeking pole arrangement. In this arrangement the individual magneticfields 42 from each element 40 transverse a closed loop with the polesof adjacent elements, and the individual fields 42 penetrate to a depthin the patient's body based on the field strength and spacing ofelements 40. The magnetic element arrangement of FIG. 10 would be mostuseful in exposing the patient 1 to a nonuniform static magnetic fieldwhich penetrates and provides strong polarizing force to only a limiteddepth within the body. It is noted that permanent magnets are currentlyavailable with various pole arrangements, such as two or more polesfacing in the same direction for example, and these alternate polearrangements may be used as elements 40.

FIG. 11 shows an embodiment of a method for exposing all, or a largeportion of, a patient's body 1 to the influence of a static magneticfield emanating from direct current electromagnet elements contained ina treatment pad 43 and driven by current from a DC power supply systemthat is connected to terminals 44 and 45. Such an embodiment will inmany cases be preferred over the use of permanent magnetic elementsbecause the properties of the magnetic field, impinging on the patientfrom treatment pad 43, may be selectively controlled or changed ifdesired by changing the current applied to terminals 44 and 45 by knowntiming, switching, and current control methods. For example, treatmentpad 43 will expose the patient's body to a nonuniform static magneticfield which can be selectively:

1. Maintained at a desired field strength level throughout thetreatment.

2. Periodically changed from one field strength level to one or moreother field strength levels throughout, or changed at any time, duringthe treatment.

3. Applied for only desired time periods throughout the treatment.

4. Periodically changed from one polarity to the other throughout, orchanged at any time during, the treatment.

5. Changed in any combination of the above at desired time periodsthroughout the treatment.

The poles of the electromagnet elements of treatment pad 43 arepreferably positioned to face the patient's body, and the coils of theelectromagnet elements may be connected so all of the same magneticpoles face in the same direction (such as all north seeking poles forexample) for maximum penetration of a strong static magnetic field intothe patient's body. Alternately, the electromagnet coils of the elementsmay be connected so the north pole of one electromagnet element isplaced next to the south pole of an adjacent electromagnet element sothe field traverses a loop between the elements, thereby limiting thedepth of penetration into the patient's body. Also, the depth andstrength of field penetration into the patient's body may be controlledby moving treatment pad 43 closer to, or further away from, the body.Also, treatment pad 43 may be placed at an angle to, instead of parallelwith, the patient.

As an option, an additional structure 46 of electromagnet elements maybe laid on or suspended above the patient and driven through terminals47 and 48 to work cooperatively with treatment paid 43 or in oppositionto it. If the individual magnetic fields produced by the electromagnetelements of structure 46 are of opposite polarity to those produced bythe electromagnet elements of treatment pad 43, the field lines connectand the patient's body is exposed to a relatively uniform staticmagnetic field. Also, structure 46 and/or treatment pad 43 may be placedat an angle to, instead of parallel with, the patent.

Selectively changing the current flow to, and/or the time that thecurrent is applied to, the electromagnet elements of treatment pad 43and structure 46 may be used to change the magnetic field influenceproduced between them, and thus through the patient's body. For example:

1. Any, or any combination of, the possible magnetic field changes notedabove for treatment pad 43 alone when supplying a nonuniform staticmagnetic field, may be achieved with the combination of treatment pad 43and structure 46 supplying a uniform magnetic field.

2. The current flow direction to treatment pad 43 and/or structure 46may be selectively changed throughout the treatment, or during desiredtime periods during the treatment, to apply a cooperative uniform staticmagnetic field to the patient for one period, and then a nonuniformstatic magnetic field may be applied by driving the treatment pad 43 andthe structure 46 in opposition for one or more additional time periodsof the treatment.

3. The electromagnet elements of treatment pad 43 and of structure 46may be activated in combination, or alternately, to expose the patientto first one type or direction of magnetic field influence, then toanother type or direction of magnetic field influence for other periodsof the treatment time. For example, treatment pad 43 may be activatedfor a period of time exposing the patient to a nonuniform staticmagnetic field, and then 46 may also be activated for one or moreperiods of time to alternately expose the patient to a uniform staticmagnetic field.

Many other operational variations are possible. Also, it is noted thatin some cases it may be desirable for structure 46 to simply be amagnetizable material instead of containing permanent or electromagnetelements. This magnetizable material would attract magnetic field linesfrom treatment pad 43 to pass through the patient's body, and structure46 may be smaller than treatment pad 43, thus attracting magnetic fieldlines from treatment pad 43 more strongly to the region of the bodyunder structure 46.

In most uses of the FIG. 11 method, the patient would be placed on thetreatment pad 43, then administered the desired bioactive agent oragents through any desired route, and then at an appropriate point intime treatment pad 43 and/or structure 46 would be activated for someperiod or some portion of the effective life of the bioactive agent toincrease the efficacy of the agent throughout the body.

FIG. 12 shows a cutaway portion of a treatment pad such as pad 43 inFIG. 11, where electromagnet elements 49 are imbedded in a soft material50, such as silicone, to maintain the relative positions of theelectromagnet elements and also to provide patient comfort (the material50 may alternately be a rigid imbedding material such as epoxy forexample). The windings of the electromagnet members 49 may be connectedso that the same magnetic poles face the patient, as shown. In thisconnection arrangement, except for areas around the edges of treatmentpad 43, the individual static magnetic fields 52 emanating from the poleof each element 49 repel the individual fields from the poles ofadjacent electromagnet elements. The individual fields thus do nottraverse a short path to terminate on the adjacent electromagnetelements, but instead penetrate deeply, or completely through, thepatient's body depending on the magnetic field strength of elements 49and the distance between the elements 49 and the patient's body.

Fabrics or other surfaces such as blankets, etc., may be placed betweensoft material 50 and the patient for patient comfort, and also softmaterial 50 will conform to the patient's body if it is placed on top ofa mattress, etc. The additional magnetic field structure 46 of FIG. 11may be constructed in the same manner as shown in FIG. 12 if thestructure 46 is to be laid on the patient. However, more control overthe applied field is achieved (as the patient moves around, etc.) bysuspending structure 46 at some desired distance above the patient, andin this instance the electromagnet elements 49 may be imbedded in, orattached to, a rigid material such as epoxy for example.

It is also noted that the invention contemplates methods in which one orthe other of treatment pad 43 and structure 46 in FIG. 11 containspermanent magnetic elements, while the other contains electromagnetelements, and/or that either treatment pad 43 or structure 46 maycontain both permanent and electromagnet elements so the field emanatingto the patient may be altered in pattern or strength by application ofcurrent to the electromagnet elements.

It is also contemplated that the invention includes methods in whichboth static magnetic and static electric elements are used together inone or more treatment elements to simultaneously or individually supplystatic magnetic and/or static electric fields.

Methods of applying properly sized and/or shaped treatment pads or otheritems containing permanent magnetic and/or electromagnetic elements toonly a desired region of the patient's body will be readily apparent inlight of the discussion of FIG. 6 and FIG. 7, and that discussion willnot be repeated here other than to note that magnetic elements may beused in place of the charged conductive elements of FIG. 6 and FIG. 7,or a combination of magnetic elements and charged conductive elementsmay be used, for exposing only a desired region of the patient's body toa magnetic, or magnetic and electric, polarizing field to increase theeffectiveness of an administered bioactive agent.

FIG. 13 shows a preferred embodiment of a method of applying a magneticfield to only a desired internal region of a patient's body 1. Magneticmicroparticles 53 may be injected, or otherwise placed, into a targetregion of the patient's body (for example into a disease site) so that abioactive agent administered to the body gains increased efficacy fromexposure to the magnetic field only in the target region of the body.Alternately, microparticles 53 may be magnetizable materials, such asparamagnetic, feromagnetic, or dimagnetic materials (from BangsLaboratories, Carmel, Ind., for example), for example, which becomemagnetic only when they are exposed to magnetic fields, and thus wouldincrease efficacy of the bioactive agents in the target site only duringthis period. Magnetic fields from another source, such as structure 54in FIG. 13, would cause the magnetizable materials to become magnetsonly while current is applied to terminals 55 and 56 of structure 54,and the time magnetized, strength, direction, and polarity of the staticmagnetic field of microparticles 53 would be controlled by structure 54.

While microparticles 53 are shown in FIG. 13, larger magnetic ormagnetizable treatment elements could be used instead. One or more ofsuch larger treatment elements can be surgically implanted or insertedinto a body cavity so as to bring the magnetic treatment element orelements as close as possible to the body target region for maximumeffect, and also to aid in continuing the effect to only the targetregion.

As an additional example of a method of applying a uniform staticmagnetic field to all, or a portion of, a patient's body, the patient,or a desired portion of the patient's body, may be placed inside of adirect current conducting coil. Passage of current through such a coilcreates a dense, uniform magnetic field through the core of the coil,and thus through the region of the patient's body within the coil. Thetime the static magnetic field is applied, the direction of the field,and the strength of the field would be controlled by known currentcontrol, switching, and timing methods.

It is noted that methods of directing, terminating, or shielding bothstatic electric and static magnetic fields are known by those skilled inthe art, and that the invention contemplates advantageously using thesemethods with the invention in desired situations. For example, in atreatment exposing external portions of the body to static electricfields, a conductive shield can be used to intercept the fields beforethey contact portions of the body not intended to be treated. Also, aconductive shield may be used to cover a portion of any treatmentelement inserted into the body to allow static electric fields to beemanated from the treatment element only in a desired area. Similarmethods, using ferrous or other magnetic field terminating materials,can also be used for magnetic treatments and elements.

The particular methods and equipment by which the invention can best beused in a particular treatment situation will depend on factors such asthe bioactive agent administered, the malady or condition to be treated,and the desired body region of the treatment. As a simplified example ofone preferred method for a particular situation, consider the treatmentof a breast cancer tumor in the upper-outer quadrant of a female breast.Assume that the tumor is discovered early and is very small, and thatthe decision is made to surgically remove just the tumor (instead of theentire breast) and to then treat the breast with at least onechemotherapeutic agent, such as adriamycin, to try to destroy anyremaining but undetectable cancer cells in the area. Adriamycin, likemost bioactive agents for treatment of neoplastic disease, is toxicenough to require intravenous injection over at least a 30 minute periodto control the blood concentration levels. Also, like most cancertreatment agents, adriamycin acts against any rapidly proliferating cellof the body, such as certain cells in bone marrow, the intestinalmucosa, testis, and hair follicles as well as cancer cells. In addition,like most cancer treatment agents, adriamycin has a relatively shorthalf-life, losing up to 50% of it's potency within 2 hours ofadministration, followed by a slower potency loss of an additional 30%within 15 to 20 hours of administration. A typical dose schedule ofadriamycin for breast carcinoma is a 30 minute i.v. injection, on eachof three days, repeated every three or four weeks. Methods of theinvention can be used in several ways to influence the treatment.

Continuing with the above example, the standard adriamycin treatmentdose and schedule would be administered with a portable polarizing field(either electric or magnetic) treatment pad such as the treatment pad 27shown in FIG. 6 adhered to each breast before beginning each injection,but with the treatment pad deactivated. Approximately 10 minutes afterstarting the injection, after the adriamycin has had time fordistribution into the breasts, the treatment pad would be activated toexpose the breasts to polarizing fields to increase the efficacy of theadriamycin against cancer cells in the breast area. The treatment padswould remain activated for 8 hours following each injection to ensurethat the applied polarizing fields were acting upon the target tissueonly while sufficient levels of adriamycin are present for maximumreaction with any cancer cells. The treatment pads would then bedeactivated and removed after 8 hours to avoid exposing the breasts topolarizing fields while only low levels of adriamycin are present. Inthis method, only the breast area of the patient would be exposed to theincreased potency of the adriamycin/polarizing field combination, andthe increased potency in the breast area would enhance the possibilityof successful treatment.

Additionally, the decision may be made to also treat the lymph nodesunder the arm adjacent to the breast since normal lymphatic drainage outof the breast occurs to these nodes, and any cancer cells leaving thebreast will likely be at least temporarily trapped in this area. In thiscase an additional treatment element may be applied under the arm toexpose the lymph nodes to polarizing fields during the treatment period.

The above noted specific suppliers, materials, methods, and embodimentsof the invention have been detailed simply to help illustrate anddescribe the invention, and are not intended to be exhaustive or tolimit the invention to the precise form or methods disclosed. Manymodifications and variations will be apparent to an ordinarily skilledperson in light of the above teaching, and it is intended that suchmodifications and variations be included in the scope of the invention.

What I claim is:
 1. A method of treating a person's body having adisease condition, the disease condition responding to a least somedegree to treatment with a therapeutic agent, the therapeutic agentbeing nonmagnetic and biologically active against the disease conditionfor a period of time, the method comprising the steps of: (a)administering the therapeutic agent to the person's body; and (b)exposing at least a portion of the person's body to a polarizing staticfield for at least a portion of the time that the therapeutic agent isbiologically active against the disease condition; wherein thepolarizing static field comprises a magnetostatic field; wherein saidstep (b) further comprises the steps of: actuating a magnetic element;including the magnetic element in a treatment element; and placing thetreatment element in a location such that the portion of the person'sbody is exposed to a magnetostatic field generated by the magneticelement; and wherein the treatment element comprises a plurality ofpermanently magnetized elements arranged such that magnetic poles of asame type point in a substantially same direction.
 2. A method oftreating a person's body having a disease condition, the diseasecondition responding to a least some degree to treatment with atherapeutic agent, the therapeutic agent being nonmagnetic andbiologically active against the disease condition for a period of time,the method comprising the steps of: (a) administering the therapeuticagent to the person's body; and (b) exposing at least a portion of theperson's body to a polarizing static field for at least a portion of thetime that the therapeutic agent is biologically active against thedisease condition; wherein the polarizing static field comprises amagnetostatic field; wherein said step (b) further comprises the stepsof: actuating a magnetic element; including the magnetic element in atreatment element; and placing the treatment element in a location suchthat the portion of the person's body is exposed to a magnetostaticfield generated by the magnetic element; and wherein the treatmentelement comprises a plurality of treatment elements, each of saidplurality of treatment elements comprising a permanently magnetizedelement, and at least one of the plurality of treatment elementscomprising a permanently magnetized element having a magnetostatic fieldpolarity that is different than a magnetostatic field polarity of othersof the plurality of treatment elements.
 3. A method of treating aperson's body having a disease condition, the disease conditionresponding to a least some degree to treatment with a therapeutic agent,the therapeutic agent being nonmagnetic and biologically active againstthe disease condition for a period of time, the method comprising thesteps of: (a) administering the therapeutic agent to the person's body;and (b) exposing at least a portion of the person's body to a polarizingstatic field for at least a portion of the time that the therapeuticagent is biologically active against the disease condition; wherein thepolarizing static field comprises a magnetostatic field; wherein saidstep (b) further comprises the steps of: actuating a magnetic element;including the magnetic element in a treatment element; and placing thetreatment element in a location such that the portion of the person'sbody is exposed to a magnetostatic field generated by the magneticelement; and wherein the treatment element comprises a plurality ofpermanently magnetized elements arranged such that magnetic poles of atleast one of the plurality of permanently magnetized elements point insome direction different than magnetic poles of a same type of others ofthe plurality of permanently magnetized elements.